Carbon Dioxide → 3-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2-thiazole-5-carboxylic acid, 4-tert-Butoxycarbonylamino-3-methyl-isothiazole-5-carboxylic acid

HRID 1782155Notes

Reaction equation

HRID 1782155 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[C:9]([CH3:13])=[N:10][S:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[C:23](=[O:25])=[O:24]>C1COCC1>[C:1]([O:5][C:6]([NH:7][C:8]1[C:9]([CH3:13])=[N:10][S:11][C:12]=1[C:23]([OH:25])=[O:24])=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 2724682Lithium diisopropylamideHCID 45790250HCID 45790250, compound

Product 1

HCID 547572143-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2-thiazole-5-carboxylic acid, 4-tert-Butoxycarbonylamino-3-methyl-isothiazole-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-methyl-isothiazol-4-yl)-carbamic acid tert-butyl ester (method 55) (21.4 g, 100 mmol) in anhydrous THF (200 mL) at -78° C., LDA (139 mL, 1.8 M solution, 250 mmol) was added dropwise over a period of 1 h. The reaction mixture was stirred at that temperature for a further 3 h after which powdered dry ice was added and the reaction slowly allowed to warm to room temperature overnight. The reaction mixture was quenched by adding saturated NH4Cl solution and extracted with ether (3×100 mL) and the combined ether layers were back extracted with satd. NaHCO3 (3×100 mL). The aqueous layers were combined and acidified to pH 5 using 6M HCl and extracted with ether (4×100 mL). The combined ether layers were dried (Na2CO3) and concentrated to give the pure acid as an off white powder. Yield 11 g (39%). 1H NMR (300 MHz) δ 1.47 (s, 9H), 2.44 (s, 3H), 8.53 (bs, 1H), 9.68 (bs, 1H).

Workup

  1. additionwas added
  2. customthe reaction
  3. customThe reaction mixture was quenched
  4. additionby adding saturated NH4Cl solution
  5. extractionextracted with ether (3×100 mL)
  6. extractionthe combined ether layers were back extracted with satd
  7. extractionextracted with ether (4×100 mL)
  8. dry with materialThe combined ether layers were dried (Na2CO3)
  9. concentrationconcentrated
  10. customto give the pure acid as an off white powder

Sources & evidence

ORD record
ord-31c4b79aa6ad465ca0f7eded1be3fab2
Source dataset
uspto-grants-2009_03
Patent number
US07498333B2

Reaction notes

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